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INTRODUCTION: A microdeletion including the SNORD116 gene (SNORD116 MD) has been shown to drive the Prader-Willi syndrome (PWS) features. PWS is a neurodevelopmental disorder clinically characterized by endocrine impairment, intellectual disability and psychiatric symptoms such as a lack of emotional regulation, impulsivity, and intense temper tantrums with outbursts. In addition, this syndrome is associated with a nutritional trajectory characterized by addiction-like behavior around food in adulthood. PWS is related to the genetic loss of expression of a minimal region that plays a potential role in epigenetic regulation. Nevertheless, the role of the SNORD116 MD in DNA methylation, as well as the impact of the oxytocin (OXT) on it, have never been investigated in human neurons. METHODS: We studied the methylation marks in induced pluripotent stem-derived dopaminergic neurons carrying a SNORD116 MD in comparison with those from an age-matched adult healthy control. We also performed identical neuron differentiation in the presence of OXT. We performed a genome-wide DNA methylation analysis from the iPSC-derived dopaminergic neurons by reduced-representation bisulfite sequencing. In addition, we performed RNA sequencing analysis in these iPSC-derived dopaminergic neurons differentiated with or without OXT. RESULTS: The analysis revealed that 153,826 cytosines were differentially methylated between SNORD116 MD neurons and control neurons. Among the differentially methylated genes, we determined a list of genes also differentially expressed. Enrichment analysis of this list encompassed the dopaminergic system with COMT and SLC6A3. COMT displayed hypermethylation and under-expression in SNORD116 MD, and SLC6A3 displayed hypomethylation and over-expression in SNORD116 MD. RT-qPCR confirmed significant over-expression of SLC6A3 in SNORD116 MD neurons. Moreover, the expression of this gene was significantly decreased in the case of OXT adjunction during the differentiation. CONCLUSION: SNORD116 MD dopaminergic neurons displayed differential methylation and expression in the COMT and SLC6A3 genes, which are related to dopaminergic clearance.
RESUMO
Este estudo objetivou analisar a compreensão dos docentes sobre suas vivências de prazer e sofrimento no trabalho. Trata-se de um estudo de caso, de natureza quantitativa e qualitativa realizado numa Instituição de Ensino Superior privada de Recife/PE. Foi aplicada a Escala de Prazer e Sofrimento no Trabalho em 100 docentes e realizadas entrevistas com cinco professores. Os dados quantitativos foram analisados com o auxílio do IBM-SPSS e as entrevistas submetidas à análise de conteúdo. Os resultados mostram vivências moderadas de sofrimento no trabalho, predominando as vivências de prazer, as quais são consequência da satisfação em desenvolver a atividade, orgulho pelo trabalho e liberdade para usar a criatividade; enquanto o sofrimento advém do esgotamento emocional e da falta de reconhecimento pelo esforço dispendido. O conteúdo das entrevistas revelou que o espaço de trabalho gera tanto sentimentos de prazer (criatividade, realização, identificação com a docência) como de sofrimento (insegurança, sobrecarga, insatisfação, frustração e injustiça).
This study aimed to analyze the teachers' understanding about their experiences of pleasure and suffering at work. This is a case study, of a quantitative and qualitative nature, carried out in a private higher education institution of Recife/PE. The Scale of Pleasure and Suffering at Work was applied to one hundred teachers and interviews were conducted with five teachers. The quantitative data were analyzed with the aid of the IBM-SPSS and the interviews were submitted to content analysis. The results show moderate experiences of suffering at work, predominating the experiences of pleasure, which are a consequence of satisfaction in developing their activity, pride in work and freedom to use creativity; while suffering comes from emotional exhaustion and lack of recognition of the effort spent. The content of the interview revealed that the work space generates both feelings of pleasure (creativity, achievement, identification with teaching) and of suffering (insecurity, overload, dissatisfaction, frustration and injustice).